Osteopathic manipulative medicine (OMM) is a body-based therapeutic approach that has been proven to be efficacious for many clinical conditions. In particular, OMM is commonly used for musculoskeletal conditions and is known to reduce pain. A theoretical foundation of OMM has long been that somato-visceral interactions also can be affected by specific OMM techniques; however, very limited data exist to support or refute this tenet. This proposal will be the first systematic series of studies that address this fundamental hypothesis. OMM techniques include 1) those directed at reducing sympathetic neural activity (SNA), or sympatholytic OMM, and 2) techniques directed at relieving pain and somatic dysfunction at the site of musculoskeletal injury. An initial study, tested the effect of sympatholytic OMM and found that basal sympathetic nerve activity (SNA) can be reduced (20-50%) in healthy subjects free of any pain syndrome. The proposed studies represent an extension of these initial findings. This project #3 will contribute to the overall goal of the proposed developmental center on the mechanisms of OMM by testing the efficacy of the two OMM modalities noted above. Pain accompanies most musculoskeletal injuries and an important part of a pain-mediated stress response is an activation of the sympathetic nervous system; thus, it follows that if OMM can reduce pain in certain conditions, it may also reduce SNA. In Study 1, intermittent cold pressor stimulus will be used to produce an experimental state of sustained elevation of SNA. We will use this condition to determine whether sympatholytic OMM can decrease a sustained elevation of SNA, and whether sustained pain-induced elevations in SNA persist when the stimulus is removed. Although hypothesized, it is not known whether OMM treatment of back pain and somatic dysfunction, can reduce SNA associated with either the pain or the somatic dysfunction. Therefore, in Study 2, it will be determined whether either OMM treatment modality can affect SNA in patients with back pain and somatic dysfunction. In addition, it will be determined whether OMM treatment effects on SNA are direct, or related to pain or somatic dysfunction. Like each of the other Units, these studies will provide critical seminal evidence regarding long-hypothesized, but under-investigated mechanisms of osteopathic manipulative medicine.